The purpose of this project is to delineate the mechanisms involved in regulating the humoral and cellular responses in patients with filariasis and other disease states. Immunoregulatory studies have examined the phenomenon of antigen-specific anergy in microfilaremic patients by showing this anergy to be a result of tolerance (by clonal deletion.) rather than active suppression. In vitro models of parasite-antigen driven antibody production as well as parasite-specific and HTLV-1 transformed T cell clones have been developed to understand in more detail those mechanisms regulating antibody production (particularly IgG and IgE) in filarial and non-filarial diseases. Recombinant lymphokines and neutralizing antibodies to them have provided additional tools for defining the mediators involved in this regulation. Qualitative analysis of filaria-specific IgE and IgG in loiasis, lymphatic filariasis, and onchocerciasis have indicated patterns of antigen recognition which differ among groups of patients with different clinical manifestations of filariasis. Using these techniques, possible vaccine targets have been identified for use in onchocerciasis.